A proof of concept trial of the anti-EGFR antibody mixture Sym004 in patients with squamous cell carcinoma of the head and neck
| Autor: | Michael Henke, Niels Jorgen Ostergaard Skartved, Pol Specenier, Rainald Knecht, P Pamperin, Thomas Gauler, Ivan D. Horak, Yassine Lalami, M-C Kaminsky, Ulrich Keilholz, J Krauß, Andreas Dietz, S Braun, Jean-Pascal Machiels |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_specialty medicine.drug_class Medizin Toxicology Monoclonal antibody Gastroenterology Disease-Free Survival Hypomagnesemia Stable Disease Cell Line Tumor Internal medicine medicine Humans Pharmacology (medical) Adverse effect Aged Aged 80 and over Pharmacology biology Squamous Cell Carcinoma of Head and Neck business.industry Pharmacology. Therapy Antibodies Monoclonal Middle Aged medicine.disease Surgery ErbB Receptors Oncology Tolerability Head and Neck Neoplasms Monoclonal Toxicity Carcinoma Squamous Cell Disease Progression biology.protein Female Human medicine Antibody business |
| Zdroj: | Cancer chemotherapy and pharmacology |
| ISSN: | 1432-0843 0344-5704 |
| Popis: | Purpose The purpose of the trial was to assess the efficacy and tolerability of Sym004, a novel 1:1 mixture of two chimeric monoclonal antibodies (992 and 1024) targeting non-overlapping epitopes of the anti-epidermal growth factor receptor (EGFR), in patients with squamous cell carcinoma of the head and neck (SCCHN). Methods Incurable, recurrent and/or metastatic SCCHN patients with acquired resistance to anti-EGFR monoclonal antibody-containing treatment received weekly infusions of 12 mg/kg Sym004 until disease progression or unacceptable toxicity. Results Among the 26 patients treated with Sym004, the proportion of patients alive without disease progression at 6 months was 12 % (95 % CI 139 %). The median duration of progression-free survival was 82 days (95 % CI 41140 days). Of 19 patients evaluable for response, eight showed a decrease in the sum of the largest diameter in their target lesions (median 11 %; range 727 %). The best overall response was stable disease in 13 patients (50 %). Paired biopsies showed a significant down-regulation of EGFR in both skin and tumors following exposure to Sym004. All patients had EGFR-related adverse events, including grade 3 skin toxicities and grade ≥3 hypomagnesemia reported in 13 (50 %) and 10 (38 %) of 26 patients, respectively. One event fulfilling the protocol-defined criteria for infusion-related reactions (grade 2) was reported. No anti-drug antibodies were detected. Conclusions The marked EGFR down-regulation shown in target tissues supports the proposed mechanism of action of Sym004. This trial revealed modest anti-tumor activity of Sym004 in extensively pretreated advanced SCCHN patients. |
| Databáze: | OpenAIRE |
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